The broad objective is to investigate the physiological stimuli and cellular mechanisms that regulate the perinatal development of aerobic metabolism in the mammalian neonate. In addition to increasing the overall capacity for cellular respiration, the neonate must adapt to a perinatal change in substrate supply from carbohydrate to fatty acids. Using the neonatal rabbit as a model, the development of several potential rate-limiting steps in the complete oxidation of fatty acids by liver mitochondria is being investigated. These include: acyl CoA synthetase, acyl CoA transferase, B oxidation of fatty acids, and respiration. Acyl CoA transferase has been found to increase shortly after birth, even in starved pups. Using the neonatal rat as a model, the postnatal maturation of oxidative phosphorylation is being examined in liver mitochondria. During the first hour after birth, State 3 respiratory rates increase with either NADH- or FADH-linked substrates, but there is no change in uncoupled respiratory rates. The postnatal development of variables which are suspected to limit State 3 respiration (such as adenine nucleotide translocase activity and the intramitochondrial adenine nucleotide content) are being studied in detail.